Both childhood adversities and mental disorders tend to be reproduced across generations, resulting in entrenched cycles of mental disorders and disadvantage. Yet this transmission timeframe? parental childhood experiences influencing mental health risk in the next generation? is only beginning to be studied in population-based human cohorts, and transmission mechanisms are not yet well understood. Early-life stress may set individuals on trajectories of suboptimal responses to later stressful life events. Mothers' own childhood adversity may therefore be associated with heightened reactions to stressors around pregnancy and childrearing. Increased worry and associated deficiency in attentional control could compromise mothers' ability to provide sensitive caregiving, a key predictor of early mental health indicators in offspring. Epigenetic markers could also signal intergenerational effects and may be important for understanding the biological aspects of mental health risk transmission and for informing intervention targets/measures. This K01 Award would extend my expertise in population-based mental health research through mentored training on bio- behavioral mental health risk transmission processes, including analysis of maternal-child interaction and epigenome-wide DNA methylation. Working with an expert mentorship team in perinatal psychobiology (Monk), vulnerable population mental health (Duarte), epigenetics (Baccarelli), and early childhood development (Hane), this proposal includes a synergistic program of coursework, intensive mentoring, and research. Leveraging a unique cohort of 2,491 Puerto Ricans followed longitudinally in San Juan and the South Bronx since the participants were children in 2000, the NIH ECHO Boricua Youth Study (5UG3OD023328-02), and adding original data collection of maternal caregiving behavior observations, the proposed research aims to determine the association between pregnant women's history of childhood adversity (measured prospectively), their worry during pregnancy about their offspring, and their early maternal caregiving sensitivity. Utilizing a dataset of genome-wide DNA methylation from 1,000 mother-infant dyads in the United Kingdom's Avon Longitudinal Study of Parents and Children, the proposed research also aims to identify specific gene loci in mothers with methylation associated with their childhood adversity, and to determine whether methylation in identified gene loci is also present in their newborn offspring. A future R01 will propose to assay and analyze biobanked DNA samples from ECHO-BYS, comparing the epigenetic findings in a more disadvantaged population, and tracking child mental health outcomes. Completion of these research aims and accompanying training will prepare me for population-based studies in which behavioral and epigenetic mechanisms are examined in tandem. This research career trajectory sets me apart as a researcher bringing translational approaches to population-based mental health work with low-resourced communities in the US and around the world, contributing to the NIMH's goal of mental health prevention research in vulnerable populations.